Intertwined Thiab Finely Balanced: Endoplasmic Reticulum Morphology, Dynamics, Function, Thiab Kab Mob Part 2

2.2. Cov qauv thiab ua haujlwm ER Subdomains

Cov txheej txheem sib txawv ntawm ER, uas yog lub luag haujlwm rau cov haujlwm tshwj xeeb, tau pom zoo txij li thawj cov duab hluav taws xob microscopy ntawm ER tau txais.

Kev sib raug zoo ntawm cov qauv tsim thiab kev nco yog ib lub ntsiab lus tseem ceeb hauv kev kawm nco. Cov yam ntxwv ntawm lub hlwb xa mus rau thaj chaw hauv lub hlwb lub luag haujlwm rau kev ua haujlwm sib txawv, xws li kev pom cov qauv ntawm lub ntsej muag, lub ntsej muag lub ntsej muag, thiab lwm yam. Vim hais tias cov txheej txheem sib txawv sib txawv ntawm cov ntaub ntawv sib txawv, lawv txoj kev ua haujlwm thiab cov cai khaws cia hauv lub hlwb kuj txawv, uas yuav cuam ​​tshuam rau kev tsim thiab tu ntawm kev nco.

Kev tshawb fawb tau pom tias cov ntaub ntawv nyob rau hauv cov txheej txheem sib txawv yog khaws cia rau hauv lub hlwb ntawm lub sijhawm tshwj xeeb thiab tom qab ntawd muab tso rau hauv, khaws cia, thiab khaws cia. Piv txwv li, cov ntaub ntawv auditory yuav tsum tau cim tam sim ntawd, thaum cov ntaub ntawv pom tau tuaj yeem nco tau qeeb. Qhov no qhia tau hais tias cov ntaub ntawv nyob rau hauv cov txheej txheem sib txawv muaj cov yam ntxwv ntawm lub cim xeeb sib txawv thiab xav tau cov tswv yim sib txawv kom nco tau.

Tsis tas li ntawd, muaj kev sib cuam tshuam ntawm cov txheej txheem sib txawv. Kev tshawb fawb qhia tau hais tias cov ntaub ntawv pom thiab hnov ​​​​lus tuaj yeem ua rau ib leeg los txhawb kev nco. Piv txwv li, thaum kawm ib lo lus, kev soj ntsuam nws cov tsos thiab kev hais lus tuaj yeem khaws cia rau hauv lub hlwb tib lub sijhawm, uas tuaj yeem ua rau kom nco tau thiab zoo ntawm lo lus.

Kev tshawb fawb tseem pom tau tias kev xav tuaj yeem cuam tshuam rau kev tsim thiab khaws cia ntawm kev nco. Lub siab lub ntsws qauv sau thiab lub cim xeeb qauv sau nyob rau hauv lub hlwb yog interconnected. Qhov nce thiab nqis ntawm kev xav yuav cuam tshuam rau cov teeb liab kis tau tus mob thiab cov ntaub ntawv ua haujlwm hauv lub hlwb, yog li cuam tshuam rau kev tsim thiab kev saib xyuas ntawm kev nco.

Yog li ntawd, txhawm rau txhim kho kev nco, peb yuav tsum nkag siab txog kev sib raug zoo ntawm cov txheej txheem sib txawv, siv cov tswv yim kev nco zoo, thiab tseem muaj lub siab zoo. Los ntawm kev kawm nquag thiab ua neej nyob, peb tuaj yeem txhim kho peb lub peev xwm nco thiab ua kom peb lub hlwb noj qab haus huv thiab muaj zog. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco, vim Cistanche deserticola muaj antioxidant, tiv thaiv kev mob, thiab tiv thaiv kev laus, uas tuaj yeem pab txo qis oxidation thiab inflammatory tshwm sim hauv lub hlwb, yog li tiv thaiv cov kab mob. kev noj qab haus huv ntawm lub paj hlwb. Tsis tas li ntawd, Cistanche deserticola kuj tseem tuaj yeem txhawb kev loj hlob thiab kho cov paj hlwb, yog li txhim kho kev sib txuas thiab kev ua haujlwm ntawm neural networks. Cov teebmeem no tuaj yeem pab txhim kho kev nco, kev kawm, thiab kev xav nrawm, thiab tseem tuaj yeem tiv thaiv kev loj hlob ntawm kev paub tsis meej thiab kab mob neurodegenerative.

Nyem Paub txhawm rau txhim kho lub cim xeeb luv luv

Nyob rau xyoo 1950, nws tau pom los ntawm George E. Palade tias ER cov nplooj ntawv zoo li yuav tsum tau studded nrog ribosomes, hu ua ntxhib ER, hos tubules feem ntau ribosome-dawb, orsmooth [46,47]. Qhov sib txawv ntawm cov qauv hauv ntau thaj tsam ntawm lub network tau ua rau muaj kev xav ntawm ER kev ua haujlwm subdomains. Txij thaum ntawd los, kev ua haujlwm tseem ceeb tau ua tiav los cuam tshuam cov morphology ntawm ER nrog nws txoj haujlwm.

2.2.1. Protein Factory thiab Kev Tswj Xyuas Zoo

Qhov zoo tshaj plaws-kev nkag siab lub luag haujlwm ntawm ER yog los ua ke thiab ntxig cov proteins rau hauv ERmembrane lossis lumen, thiab qhov no tshwm sim feem ntau los ntawm ribosomes koom nrog lub ntsej muag cytosolic ntawm ER, qhov twg cov saw hlau tshiab polypeptide yog translocated dhau ntawm Sec61 translocon, raws li kev tshuaj xyuas. qhov teeb meem tshwj xeeb los ntawm Sicking et al. [48].

InS. Cerevisiae, daim ntawv ribosome ceev tau pom tias loj dua tubule ribosome ntom [49]. Raws li ribosomes txuas rau ER kom tso cai rau kev txhais lus ntawm secretedor membrane-bound proteins, qhov tshwm sim, nrog rau cov txiaj ntsig ntawm electron microscopystudies xws li cov los ntawm Palade [46,47], coj mus rau lub tswv yim tias cov nplooj ntawv yog qhov chaw tseem ceeb rau cov protein biosynthesis. hauv ER. Qhov tsis tshua muaj daim nyias nyias curvature thiab loj lumenalvolume ntawm nplooj ntawv yog qhov zoo rau ob qho tib si khi ntawm ribosomes los yog polyribosomes rau thebilayer thiab rau kev nkag tau ntawm chaperones rau nascent peptides xav tau rau folding thiab post-translational modifications.

Nyob rau hauv kev pom zoo nrog lub tswv yim hais tias ribosome-studded sheets ntawm ntxhib ER tsim ib tug "protein Hoobkas" functional domain, hlwb uas tshwj xeeb nyob rau hauv secreting proteins, xws li pancreatic secretory hlwb, muaj ib tug ntau dua feem ntawm ER nplooj ntawv tshaj cell uas secrete tsawg heev proteins, xws li raws li epithelial hlwb thiab neurons [50] Cheebtsam ntawm translocon kuj tau ntxiv rau hauv nplooj ntawv [13].

Ua ke, cov txiaj ntsig no tau pom zoo tias cov ntawv txheeb yog qhov chaw tseem ceeb ntawm cov protein biosynthesis hauv ER.Tshiab synthesized membrane thiab lumenal proteins yuav tsum tau quav kom zoo thiab kho kom zoo tom qab kev txhais lus, piv txwv li los ntawm kev sib ntxiv thiab tom qab ntawm glycan chains thiab tsim ntawm disulfide txuas hniav (saib hauv [51,52]).

Cov txheej txheem no suav nrog ntau tus neeg nyob hauv ER-chaperones thiab cov enzymes uas ua raws li kev pabcuam thiab saib xyuas qhov tseeb folding thiab glycosylation raws li txoj cai los ntawm lub voj voog thecalnexin / calreticulin. Txhua cov proteins uas tsis quav ntsej raug lees paub thiab tshem tawm ntawm lub voj voog no, kom rov qab mus rau hauv ER thiab degraded los ntawm cov proteasome nyob rau hauv ib tug txheej txheem ER-koom nrog degradation (ERAD) [51].

Lub load ntawm misfolded proteins yog nyob ze saib xyuas, thiab yog hais tias muaj ntau dhau lawm, lub unfolded protein teb (UPR) yog tshwm sim, uas ua rau upregulation ntawm lub tseem ceeb ER-nyob proteins uas yuav tsum tau rau protein folding ua ke nrog inhibition nyob rau hauv protein synthesis [53].

Thaum cov proteins koom nrog hauv folding thiab glycan ntxiv tau muab faib thoob plaws hauv ER, muaj pov thawj tias qee cov proteins tseem ceeb hauv kev tswj kom zoo thiab ERAD txoj hauv kev yuav muaj cov qauv tshwj xeeb hu ua ER-derived quality control compartment (ERQC) uas nyob ib sab ntawm lub nucleus. [52]. Txawm hais tias qhov tseeb ntawm qhov chaw no thiab yuav ua li cas itis txuas nrog cov ER loj tseem tsis meej, nws qhov chaw nyob yog nyob ntawm microtubulemotor dynein [54].

Interestingly, ntev ER kev ntxhov siab tau pom los ua rau muaj kev rov qab tsim ntawm whorls ntawm ribosome-dawb ER daim nyias nyias uas muaj Sec61 translocon thiab keyUPR signaling enzyme PKR-zoo li ER kinase (PERK), tab sis tsis yog reticulons, CLIMP63 lossis thelumenal marker [55 calreticulin. ]. Lub whorls tsim los ntawm vesicular / tubular structuresthat budded los ntawm ER ntawm txoj kev COPII (saib hauv qab) thiab tom qab fusedand flattened. Qhov no yog qhov txawv ntawm qhov ib txwm muaj, qhov twg Sec61 raug cais tawm ntawm COPII vesicles.

Cov whorls no tuaj yeem pab txhawb ob qhov txiaj ntsig UPR: inhibition ntawm proteintranslocation los ntawm kev cais thiab inactivating translocons, thiab ua kom PERK. Thewhorls zoo li lub koom haum ER (OSER) yav dhau los pom thaum qee cov ER proteins xws li HMG-CoA reductase lossis cytochrome b5 tau tshaj tawm [56,57]. Yuav ua li cas whorlsand OSER cuam tshuam rau ERQC yog cov lus nug tseem ceeb uas yuav tsum tau hais rau yav tom ntej.

2.2.2. ERES: Export Checks

Kho qhov lumenal thiab membrane proteins tawm ntawm ER ntawm ER tawm qhov chaw (ERES), uas yog cov qauv sib txawv, ribosome-dawb puncta nyob rau hauv cov ntxhib ER network.

Cov chaw tawm muaj xws li ib pawg ntawm vesicular-tubular membranes [58,59], txuas ntxiv nrog ER membrane. Nyob rau hauv vertebrate hlwb, ERES tau tawg thoob plaws hauv lub network, thiab cov protein hloov ntawm ER mus rau Golgi tso siab rau microtubule-dependent thauj ntawm thedynein / dynactin motor protein complex [60]. Lub ERES lawv tus kheej tau ua haujlwm luv luv ntawm microtubules [61].

Ob lub tsho tiv thaiv protein ntau, COPI thiab COPII, pab hauv kev tsim thiab kev koom tes ntawm qhov chaw tawm thiab hauv kev thauj cov protein. COPII formsa scaffold rau deform daim nyias nyias, tswj cov khoom thauj nkag mus rau hauv ERES [62], thiab tseem nyob hauv ERES txawm tias tom qab cov khoom thauj tau tawm mus [63–65]. COPI txawm li cas los xij, taug kev nrog cov khoom thauj thaum nws thauj mus los ntawm qhov chaw tawm [66], zoo li Rab1 [65]. Lub luag haujlwm tseeb ntawm COPI hauv kev thauj khoom thauj mus deb ntawm ER tsis paub, tab sis nws tuaj yeem ua lub luag haujlwm hauv kev txheeb xyuas thiab xa cov khoom thauj mus rau Golgi apparatus [66,67].

Cov qauv kev txiav txim siab dua ntawm ERES tsuas yog tsis ntev los no tau txheeb xyuas siv FIB-SEM.Weigel li al. tshawb pom tias ib qho kev sib txuas ntawm cov tubules nqaim (40–60 nm indiameter) muaj nyob ntawm qhov chaw tawm, txuas nrog ER los ntawm lub caj dab me me COPII [63].Long, pearling tubules nrog COPI punctae kuj pom tau los ntawm qhov chaw tawm. , nrog microtubules mus rau Golgi apparatus.

Pearled outlines yog cov cim ntawm qhov ntev ntawm qhov nro hauv tubular daim nyias nyias [68] thiab tej zaum yuav yog qhov tshwm sim ntawm cov rog siv los ntawm dynein / dynactin [60]. Xws li daim nyias nyias pearling tau pom tias yog precursorto fission, hloov cov tubules rau hauv vesicles [69].

Dynein tuaj yeem raug xaiv rau ERESmembranes los ntawm kev sib cuam tshuam ntawm dynactin p150 thiab COPII Cheebtsam Sec23 thiab Sec24 [70], tab sis yuav ua li cas lub cev muaj zog txuas rau cov neeg nqa khoom thaum lub tsho ploj lawm yog ib qho lus nug qhib. Ib txoj hauv kev muaj peev xwm yog los ntawm BicD2 thiab Rab6, uas tau pom tias recruitdynein rau ERES thiab tsav lawv cov concentration hauv thaj tsam perinuclear [59].

Kinesin{0}} kuj tseem muaj nyob rau ntawm ob qho tib si ERES [61] thiab cov neeg nqa khoom thauj lawv tsim [71]. Interestingly, qhov chaw tawm kuj pom muaj ob npaug ntawm txoj kab uas hla nyob rau hauv cov lus teb rau tsub zuj zuj ntawm cargo, thaum lub cheeb ntawm nyob ze ER tubules tsis cuam tshuam [63]. Ua ke, cov kev tshawb fawb no qhia tau hais tias ER qhov chaw tawm yog cov khoom thauj khoom xa tawm tau zoo heev, muaj peev xwm los teb cov kev hloov pauv hauv xov tooj ntawm tes.

2.2.3. MCSs: Lipid Chaw tsim tshuaj paus

Muab hais tias cov ntawv txheeb yuav muaj lub luag haujlwm rau cov protein biosynthesis, tubules puas tuaj yeem ua lub luag haujlwm rau lipid synthesis thiab calcium ion homeostasis? Hauv kev txhawb nqa ntawm lub tswv yim no, lub luag haujlwm ntawm cov tshuaj steroid synthesis, xws li adrenal cortical hlwb, muaj feem ntau ribosome-free smooth ER [72].

Nws kuj tau pom zoo tias cov chaw sib cuag ntawm daim nyias nyias (MCSs) ntawm ER thiab lwm yam organelles yuav muaj ntau dua hauv thaj tsam ribosome-freetubular ntawm lub network, tshwj xeeb tshaj yog cov MCSs tsim nrog cov plasma membrane, endosomes, lipid droplets, thiab mitochondria [73] —78]. MCSs thiab cov proteins uas cuam tshuam tau tham hauv qhov kev tshuaj xyuas no tau qhia hauv daim duab 2.

MCSs yog tethered kev sib txuas ntawm organelles, qhov uas cov membranes tsis fused, tab sis sib cais los ntawm 5-30 nm [79-82]. Xws li qhov sib thooj ntawm daim nyias nyias ua rau cov tsis-vesicular hloov ntawm cov khoom thauj ntawm cov organelles [83]. MCSs muaj nyob nruab nrab ntawm ER thiab yuav luag txhua lwm subcellularorganelle [38,81]. Lawv muaj nuj nqi, morphology, thiab dynamics muaj ntau haiv neeg thiab zoo tshuaj xyuas (xws li, [84–{10}}]).

Ntawm no, peb yuav tsom mus rau cov kev sib txuas ntawm MCSs thiab ER muaj nuj nqi thiab dynamics.Lipid biosynthesis paub tias tshwm sim feem ntau hauv ER [87,88]. Siv cov cell fractionation, enrichment ntawm cov tshuab koom nrog hauv lipid thiab sterol synthesis tau pom nyob rau hauv ER membrane uas yog txuam nrog mitochondria [89-91] thiab plasma membrane [92]. 

Tsis ntev los no, nws tau pom tias ER-plasma membrane tiv tauj qhov chaw yuav tsum tau rau kev sib txuas ntawm phosphatidylcholine, ib qho tseem ceeb ntawm cov kab mob lom, hauv cov poov xab [93]. Lipid metabolizing machinery kuj tau pom nyob rau ntawm ntug ntawm dynamic ER tubules [7] thiab nyob rau hauv dynamic ER-derived vesicles uas tiv nrog ntau lwm yam organelles hauv Cos -7 hlwb [94].

ER kuj yog lub luag haujlwm rau kev sib txuas ntawm cov lipids nruab nrab [95]. Cov lipids nruab nrab tsis muaj cov pab pawg them nyiaj thiab yog li tsis tuaj yeem yooj yim muab tso rau hauv lipid bilayers. Xwb, lipid droplets yog tsim, uas muaj cov aphospholipid monolayer nyob ib ncig ntawm lub hauv paus ntawm nruab nrab lipids. Cov ntsiab lus tseeb txog kev tsim cov lipid tee dej tseem tab tom sib cav; Txawm li cas los xij, tam sim no nws paub tias lipiddroplets tau tsim hauv ER [96-98].

Cov lipids nruab nrab sib sau ua ke nyob rau hauv lipid bilayer ntawm ER, tsim ib lub lens ntawm sab hauv thiab sab nrauv nplooj ntawv [97], ua ntej budding tawm mus rau hauv lub cytoplasm [99]. Hauv cov nroj tsuag, nws kuj tau pom tias cov lipid droplets yog tsim nyob rau hauv tshwj xeeb subdomains ntawm ER [100]. Kuv

Ntxiv nrog rau kev tsim hauv ER, lipiddroplets tuaj yeem rov hu rau ER thaum lawv tau tawg tawm [101]. ER-lipid dropletmembrane txuas hniav tsim tau npaj los pab txhawb kev sib pauv ntawm lipid metabolizingenzymes, yam tsis muaj cov lipid loj tsis tsim [102-104].

Qhov kev tshawb pom ntawm kev tswj cov lipid metabolizing tshuab nyob rau hauv tubular ER, tshwj xeeb tshaj yog nyob rau hauv MCSs nrog cov plasma membrane, mitochondria, thiab lipid droplets, qhia tias cov subdomains kuj koom nrog hauv lipid metabolism [7,89–92,94,95].

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